CCTN - CONTRACEPTIVE EFFICACY AND SAFETY OF DAILY ORAL ULIPRISTAL ACETATE

CCTN - 每日口服醋酸乌利司他的避孕功效和安全性

• 批准号: 8729747
• 金额: $ 87.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-16 至 2016-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8729747
• 关键词: Acetates; Adherence; Adverse effects; Affect; Age; Amenorrhea; Child; Child health care; Clinical Trials; Clinical Trials Network; Contraceptive Agents; Contraceptive methods; Dose; Drug Kinetics; Estrogens; Hemorrhage; Human Development; In Vitro; Institutes; Interruption; Menstrual cycle; Methods; Mission; National Institute of Child Health and Human Development; Non obese; Obesity; Oral; Oral Contraceptives; Ovulation; Pattern; Pharmacodynamics; Population; Progesterone Receptors; Progestins; Public Health; Randomized; Regimen; Risk; Safety; Thromboembolism; Time; United States Food and Drug Administration; Uterine Fibroids; Venous; Woman; arm; contraceptive efficacy; emergency contraception; malignant breast neoplasm; pill; reproductive

There is a demand for estrogen-free contraception in order to reduce the risk of venous thromboembolism (VTE), particularly for obese women. A new oral contraceptive agent consisting of a progesterone receptor modulator, which does not affect endogenous estrogen levels, has been developed. Ulipristal acetate (UPA) has been used in a single high dose for emergency contraception and has been used continuously for up to six months for treatment of uterine fibroids. Low dose continuous usage of oral UPA is anticipated to inhibit ovulation and provide an estrogen free, bleed free method of contraception. The Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) has a mission to develop safe and effective contraceptives for women, including obese women. Obesity is the number one public health issue facing the US population and is an independent risk for venous thromboembolism (VTE). Therefore, there is a public health need to develop effective contraception for woman that does not increase the risk of VTE. One Food and Drug Administration (FDA)-approved contraceptive method is the progestin-only pill (POP). This method requires strict adherence to taking the POP at the same time every day. The method is associated with irregular bleeding which often leads to discontinuation of the method. Daily low dose oral progesterone receptor modulators (PRMs), such as UPA, have been shown to inhibit ovulation and cause amenorrhea. The endogenous estrogen level is not affected by the PRM. Thus, the method will provide a regimen that is easier to follow than POP regimen and have a theoretically lower risk of VTE, especially for obese women. In addition, there is in vitro evidence that UPA may have protective activity against breast cancer. In order to provide preliminary evidence that daily, low dose UPA could be effective for contraception, a clinical trial will be conducted in the NICHD Contraceptive Clinical Trials Network (CCTN). The proposed study will be evaluated sequentially. Initially, women of reproductive age, with normal menstrual cycles, will receive treatment for 12 weeks (three 28-day cycles) in order to evaluate the mechanisms of contraceptive efficacy, safety and acceptability of this new contraceptive.

为了降低静脉血栓栓塞（VTE）的风险，特别是对于肥胖妇女，需要无雌激素的避孕措施。已经开发了一种由孕酮受体调节剂组成的新的口服避孕剂，不影响内源性雌激素水平。乙酸乌统（UPA）已在单剂量中用于紧急避孕剂，并已连续使用长达六个月的子宫肌瘤治疗。预计口服UPA的低剂量连续使用将抑制排卵，并提供不含雌激素的，无血出血的自由避孕方法。 Eunice Kennedy Shriver国家儿童健康与人类发展研究所（NICHD）的使命是为包括肥胖妇女在内的妇女开发安全有效的避孕药具。肥胖是美国人口面临的第一公共卫生问题，是静脉血栓栓塞（VTE）的独立风险。因此，公共卫生需要为不增加VTE风险的女性开发有效的避孕。一种食品药品监督管理局（FDA）批准的避孕方法是仅孕激素药（POP）。这种方法需要严格遵守每天同时进行流行。该方法与不规则的出血有关，这通常会导致该方法中断。每日低剂量的口服孕激素受体调节剂（PRMS）（例如UPA）已被证明会抑制排卵并引起闭经。内源性雌激素水平不受PRM的影响。因此，该方法将提供一种比流行方案更容易遵循的方案，并且理论上VTE的风险较低，尤其是对于肥胖妇女而言。此外，有体外证据表明UPA可能具有针对乳腺癌的保护活性。为了提供初步证据表明，每天，低剂量UPA可能对避孕有效，将在NICHD避孕试验网络（CCTN）中进行临床试验。拟议的研究将依次评估。最初，具有正常月经周期的生殖年龄妇女将接受12周（三个28天周期）的治疗，以评估这种新避孕药的避孕功效，安全性和可接受性的机制。